title: Ccr5 deficiency regulates the proliferation and trafficking of natural killer cells under physiological conditions.
abstract: Chemokines were shown to govern the trafficking of immune cells and may also play important roles in the survival and activation of these cells. We report here that under physiological conditions, the bone marrow (BM), spleen, blood and liver of Ccr5, but not of Ccr1-deficient mice, contain reduced numbers of NK cells. NK cells in the BM of Ccr5-deficient mice proliferate to a lesser extent compared to WT mice. Furthermore, spleen NK cells derived from Ccr5-deficient mice that were transplanted into irradiated recipients failed to proliferate in the host. Ccr5, but not Ccr1-deficient NK cells, failed to migrate in vitro in response to RANTES and MIP-1β but not MIP-1β or SDF-1 and had reduced activation, lower expression levels of NK cell markers and a slightly reduced capacity to adhere to target cells and stimulate their killing. Using the polyI:C mouse model for NK trafficking, we found that in the absence of Ccr5, but not Ccr1, NK cells failed to accumulate in the liver. In contrast, using the influenza viral infection as a model to evaluate NK cell proliferation, we found that Ccr5-deficient NK cells in the BM had a higher proliferation rate than WT NK cells. These results suggest a role for Ccr5 in NK cell proliferation and circulation under physiological conditions and a complex role for Ccr5 in determining the fate of NK cells under pathological conditions.
authors.affiliation: Goldyne Savad Institute of Gene Therapy, Hadassah University Hospital, P.O. Box 12000, Jerusalem 91120, Israel.
authors.forename: Ido D
authors.initials: ID
authors.lastname: Weiss
authors.forename: Hadas
authors.initials: H
authors.lastname: Shoham
authors.forename: Ori
authors.initials: O
authors.lastname: Wald
authors.forename: Hanna
authors.initials: H
authors.lastname: Wald
authors.forename: Katia
authors.initials: K
authors.lastname: Beider
authors.forename: Michal
authors.initials: M
authors.lastname: Abraham
authors.forename: Neta
authors.initials: N
authors.lastname: Barashi
authors.forename: Eithan
authors.initials: E
authors.lastname: Galun
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.forename: Amnon
authors.initials: A
authors.lastname: Peled
mesh_terms: D000818:Animals; D017209:Apoptosis; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D010641:Phenotype; D011070:Poly I-C / Q000378:metabolism; D019713:Receptors, CCR5 / Q000172:deficiency* / Q000502:physiology*; D013154:Spleen / Q000378:metabolism; D014777:Virus Diseases / Q000378:metabolism
chemical_list: D019713:Receptors, CCR5; D007371:Interferon-gamma; D011070:Poly I-C